Abstract
Quorum-sensing systems mediate chemical communication between bacterial cells, coordinating cell-density-dependent processes like biofilm formation and virulence-factor expression. In the proteobacterial LuxI/LuxR quorum sensing paradigm, a signaling molecule generated by an enzyme (LuxI) diffuses between cells and allosterically stimulates a transcriptional regulator (LuxR) to activate its cognate promoter (pR). By expressing either LuxI or LuxR in positive feedback from pR, these versatile systems can generate smooth (monostable) or abrupt (bistable) density-dependent responses to suit the ecological context. Here we combine theory and experiment to demonstrate that the promoter logic of pR – its measured activity as a function of LuxI and LuxR levels – contains all the biochemical information required to quantitatively predict the responses of such feedback loops. The interplay of promoter logic with feedback topology underlies the versatility of the LuxI/LuxR paradigm: LuxR and LuxI positive-feedback systems show dramatically different responses, while a dual positive/negative-feedback system displays synchronized oscillations. These results highlight the dual utility of promoter logic: to probe microscopic parameters and predict macroscopic phenotype.
Highlights
Free-living bacteria use quorum-sensing systems – dedicated chemical communication channels – to coordinate populationwide behaviors [1,2]
In many gram-negative bacteria, quorum sensing is mediated by two key proteins termed LuxI and LuxR, and a class of signaling molecules known as acylhomoserine lactones (AHLs) [1]
Using a combination of theory and experiment, we show how the promoter logic function of pR is defined and measured; we describe how to predict density-dependent responses from this measurement alone; and we successfully predict the responses of several distinct feedback systems built from V. fischeri LuxI/LuxR components
Summary
Free-living bacteria use quorum-sensing systems – dedicated chemical communication channels – to coordinate populationwide behaviors [1,2]. These systems regulate the cell-densitydependence of several bacterial activities, including bioluminescence, competence and sporulation, biofilm formation, and virulence factor expression [3,4]. AHL-bound LuxR activates transcription at the pR promoter; this initiates a positive-feedback loop via LuxI synthesis. In order to understand this interplay it seems we must first comprehensively characterize a vast number of relevant parameters – species concentrations, reaction rates, binding constants, and so on This expanse of biochemical detail presents a fundamental barrier to developing a predictive, experimentally falsifiable description of these systems
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